The activity of fatty acid synthase of epidermal keratinocytes is regulated in the lower stratum spinousum and the stratum basale by local inflammation rather than by circulating hormones

Abstract

The epidermal keratinocytes produce and secrete lipids to maintain the water barrier of the epidermis. To clarify the regulation of epidermal lipid synthesis, we investigated the hormonal effect on the activity of fatty acid synthase (FAS) of the keratinocytes, and the expression of FAS in the human skin. In cultured keratinocytes, the FAS activity, assayed by measuring the oxidation of NADPH, was slightly increased by hydrocortisone or testosterone, but not influenced by thyroid hormone, estrogen, progesterone or insulin. In immunohistochemical study of normal human epidermis, FAS was expressed strongly in the stratum granulosum and moderately in the uppermost layer of the stratum spinousum (SS), suggesting that fatty acid synthesis may increase during normal epidermal differentiation. In inflammatory disorders, such as psoriasis, lichen planus, and atopic dermatitis, FAS was also expressed in the lower SS and the stratum basale (SB), resulting in strong staining in the whole layers of the epidermis. Remarkable increase of FAS expression was only observed in the lower SS and the SB. Therefore, the activity of FAS in the epidermis may be regulated in the lower SS and the SB by local inflammation rather than by circulating hormones. In other components of the skin, FAS was strongly expressed not only in adipose tissue and sebaceous glands, which are known as active sites of lipid synthesis, but also in sweat glands, suggesting that the sweat glands can synthesize abundant fatty acids de novo.